Three years ago, we had sufficient preliminary data to suggest that we could isolate an osteochondral progenitor cell from bone marrow, which we refer to as a Mesenchymal Stem Cell. We have now firmly established that we can isolate such progenitor cells, that such cells can proliferate in cell culture and can be passaged and, lastly, that such cells can be tracked to demonstrate their involvement in osteogenesis. Based on our demonstrated progress to isolate, culture and mitotically expand these cells, we specifically propose to mark clones of these cells to directly determine if the descendants of the marked cells become integrated into only one tissue (committed progenitors) or into many mesenchymal tissues (a stem cell) . Such marking can be accomplished by use of plasmids or retrovirus which have the bacterial beta-galactosidase gene whose transcription product will provide a reporter (stainable) enzyme marker. In addition, by comparing young and old recipients of the marked cells, it will be possible to compare the progenitor cell dynamics in both growing and maintenance activities of skeletal tissues. Whether or not these marrow-derived mesenchymal cells are stem cells or not, we propose to use these culture-expanded cells in a massive bone excision model to effect repair/regeneration of a femoral gap in the rat. The use of porous calcium phosphate ceramics as both a delivery vehicle for culture-expanded cells and as a scaffolding on which new bone can be quickly fabricated is also proposed in parallel to the marking experiments. Both of these projects have considerable utility in understanding aspects of skeletal development and repair.